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Clinical Trial Details — Status: Active, not recruiting

Administrative data

NCT number NCT04182204
Other study ID # MO40598
Secondary ID 2018-003727-10
Status Active, not recruiting
Phase Phase 3
First received
Last updated
Start date February 7, 2020
Est. completion date March 30, 2025

Study information

Verified date April 2024
Source Hoffmann-La Roche
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

This study is a multicenter, open-label study of polatuzumab vedotin administered by intravenous (IV) infusion in combination with rituximab, gemcitabine and oxaliplatin (R-GemOx) in participants with relapsed or refractory diffuse large B-cell lymphoma (DLBCL). The study comprises of two stages: a safety run-in stage and a randomized controlled trial (RCT).


Description:

The safety run-in stage (Stage 1) will assess the safety of polatuzumab vedotin plus rituximab, gemcitabine and oxaliplatin (Pola-R-GemOx) in 10 participants. The randomized controlled trial (RCT) (Stage 2) will compare Pola-R-GemOx versus R-GemOx alone using overall survival (OS). This is an event-driven trial.


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Study Design


Intervention

Drug:
Polatuzumab Vedotin
Polatuzumab vedotin 1.8 mg/kg for a maximum dose of 240 mg/cycle IV on Day 1 of each 21-day cycle for up to 8 cycles.
Rituximab
Rituximab 375 mg/m2 IV on Day 1 of each 21-day cycle for up to 8 cycles.
Gemcitabine
Gemcitabine 1000 mg/m2 IV on Day 2 of each 21-day cycle for up to 8 cycles.
Oxaliplatin
Oxaliplatin 100 mg/m2 IV on Day 2 of each 21-day cycle for up to 8 cycle.

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Sponsors (1)

Lead Sponsor Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

United States,  Brazil,  Canada,  China,  Finland,  France,  Germany,  Greece,  India,  Ireland,  Italy,  Korea, Republic of,  Mexico,  Spain,  Turkey,  United Kingdom, 

Outcome

Type Measure Description Time frame Safety issue
Other Stage 1: Observed Plasma Concentrations of Polatuzumab Vedotin Antibody-Conjugated Mono-Methyl Auristatin E (acMMAE) and Unconjugated MMAE (ng/mL) Re-classified as 'Other Pre-specified' due to sparse PK sampling, to support population PK analysis of the data which is an exploratory analysis. Pre- and post-dose (infusion duration=90 minutes [min]) on Cycle 1 Day 1 and Cycle 4 Day 1 (Cycle length=21 days)
Other Stage 2: Observed Plasma Concentrations of Polatuzumab Vedotin Antibody-Conjugated Mono-Methyl Auristatin E (acMMAE) and Unconjugated MMAE (ng/mL) Re-classified as 'Other Pre-specified' due to sparse PK sampling, to support population PK analysis of the data which is an exploratory analysis. Pre- and post-dose (infusion duration=90 minutes [min]) on Cycle 1 Day 1 and Cycle 4 Day 1 (Cycle length=21 days)
Primary Stage 1: Percentage of Participants with Adverse Events (AEs) From baseline until 90 days after last dose (up to approximately 55 months)
Primary Stage 2: Overall Survival (OS) Overall survival was defined as the time from the date of randomization to the date of death from any cause. From randomization in RCT up to approximately 34 months
Secondary Stage 1: Percentage of Participants with Peripheral Neuropathy Peripheral neuropathy will be measured by the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity 12-Item Scale (FACT-GOG/Ntx12). FACT-GOG/Ntx12 is a 12-item self-reported questionnaire designed to measure chemotherapy-induced peripheral neuropathy and contains 12 items, covering sensory neuropathy, motor neuropathy, hearing neuropathy, and dysfunction associated with neuropathy. From baseline up to approximately 71 months
Secondary Stage 1: Percentage of Participants with Polatuzumab Vedotin Dose Interruptions and Dose Reductions From baseline up to approx. 55 months
Secondary Stage 1: Polatuzumab Vedotin Dose Intensity Dose intensity is defined as the ratio of actual dose administered versus intended dose. From baseline up to approx. 55 months
Secondary Stage 1: Percentage of Participants with Anti-drug Antibodies (ADAs) to Polatuzumab Vedotin at Baseline Baseline (Day 1 of Stage 1)
Secondary Stage 1: Percentage of Participants with Anti-drug Antibodies (ADAs) to Polatuzumab Vedotin Post-Baseline Baseline up until Month 2 of the Post-Treatment Follow-up period (up to approx. 55 months)
Secondary Stage 1: Percentage of Participants with Complete Response (CR) CR was defined as complete metabolic response assessed by the investigator through PET-CT Scan according to Lugano 2014 response criteria. From baseline up to approximately 55 months
Secondary Stage 1: Percentage of Participants with Objective Response (OR) OR is defined as complete metabolic response (CR) or partial metabolic response (PR) and will be assessed by the investigator through PET-CT scan according to Lugano 2014 response criteria. From baseline up to approximately 55 months
Secondary Stage 1: Best Overall Response (BOR) BOR is defined as the best response recorded from the start of treatment until end of treatment (based on PET-CT or CT data) according to Lugano 2014 response criteria, determined by the investigator From baseline up to approximately 71 months
Secondary Stage 1: Progression Free Survival (PFS) PFS is defined as the time from enrollment to the first occurrence of disease progression (as determined by the investigator according to Lugano 2014 response criteria) or death. From baseline up to approximately 71 months
Secondary Stage 1: Overall Survival (OS) OS is defined as the time from enrollment to death from any cause. From baseline up to approximately 71 months
Secondary Stage 1: Event Free Survival (EFS) EFS is defined as the time from enrollment to the first occurrence of disease progression or relapse, death due to any cause or initiation of any non-protocol-specified antilymphoma treatment (NALT). From baseline up to approximately 71 months
Secondary Stage 2: Percentage of Participants with Objective Response (OR) OR is defined as CR or PR and will be assessed by an Independent review committee through PET-CT scan according to Lugano 2014 response criteria.
OR will also be assessed by the investigator using Response alone (not including PET data) and will consider complete response instead of complete metabolic response.
From randomization in RCT until up to 34 months
Secondary Stage 2: Percentage of Participants with Complete Response (CR) CR will be assessed by an Independent review committee through PET-CT scan according to Lugano 2014 response criteria.
CR will also be assessed by the Investigator using Response (not including PET data) and will consider complete response instead of complete metabolic response.
From randomization in RCT until up to 34 months
Secondary Stage 2: Best Overall Response (BOR) BOR is defined as the best response recorded from the start of treatment until end of treatment (based on PET-CT or CT data) according to Lugano 2014 response criteria, determined by the investigator From randomization in RCT until up to 49 months
Secondary Stage 2: Progression Free Survival (PFS) PFS is defined as the time from the time of randomization to the first occurrence of disease progression (as determined by the investigator according to Lugano 2014 response criteria) or death. From randomization in RCT until up to 49 months
Secondary Stage 2: Duration of Response (DOR) DOR will be assessed in patients who had an OR, as determined by the investigator, using Lugano 2014 response criteria. DOR is defined as the time interval from the date of the first occurrence of a CR or PR (whichever status is recorded first) until the first date that progressive disease or death is documented, whichever occurs first. From randomization in RCT until up to 49 months
Secondary Stage 2: Event Free Survival (EFS) EFS is defined as the time from enrollment to the first occurrence of disease progression or relapse, death due to any cause or initiation of NALT. From randomization in RCT until up to 49 months
Secondary Stage 2: Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality-of-Life Questionnaire Core 30 (QLQ-C30) Score The EORTC QLQ-C30 includes five functional scales (physical, role, cognitive, emotional, social); a global health status (GHS)/quality of life (QoL) scale; and items measuring fatigue, pain, nausea and vomiting, dyspnea, appetite loss, sleep disturbance, constipation, diarrhea, and financial difficulties. The score range for each scale and single-item measure is 0 to 100, where higher scores indicate a higher response level (i.e., better functioning, better QoL, worse symptoms). Key scales included physical functioning, and fatigue, and GHS. Baseline (Cycle 1 [each cycle is 21 days]), Cycles 2, 3, 5, and 7; 28 days after last dose; and every 2 months during follow up (up to 49 months)
Secondary Stage 2: Time to Deterioration in Physical Functioning and Fatigue Time to deterioration in physical functioning and fatigue is defined as the time from randomization to the first documentation of a 10-point decrease in EORTC QLQ-C30 physical functioning and fatigue scales from baseline. The EORTC QLQ-C30 includes five functional scales (physical, role, cognitive, emotional, social); a global health status (GHS)/quality of life (QoL) scale; and items measuring fatigue, pain, nausea and vomiting, dyspnea, appetite loss, sleep disturbance, constipation, diarrhea, and financial difficulties. The score range for each scale and single-item measure is 0 to 100, where higher scores indicate a higher response level (i.e., better functioning, better QoL, worse symptoms). Key scales included physical functioning, and fatigue, and GHS. Baseline (Cycle 1 [each cycle is 21 days]), Cycles 2, 3, 5, and 7; 28 days after last dose; and every 2 months during follow up (up to 49 months)
Secondary Stage 2: Change From Baseline in Functional Assessment of Cancer Therapy-Lymphoma (FACT-Lym) Total Score The FACT-Lym is a validated health-related quality of life (HRQoL) instrument used specifically in patients with lymphoma. It is composed of the 27-item FACT-general questionnaire (FACT-G), which measures health-related quality of life in patients undergoing any type of cancer therapy, plus the 15-item Lymphoma-Specific Subscale (FACT-Lym LYMS), which assesses the HRQoL impacts of more lymphoma-specific symptoms. Each item of the FACT-Lym is answered using a 5-point scale ranging from 0 = "not at all" to 4 = "very much". 0 = Not at all, 1 = a little bit, 2 = somewhat, 3 = quite a bit, and 4 = Very much. FACT-LYM total score can be calculated and higher scores are reflective of better HRQoL. Baseline (Cycle 1 [each cycle is 21 days]), Cycles 2, 3, 5, and 7; 28 days after last dose; and every 2 months during follow up (up to 49 months)
Secondary Stage 2: Time to Progression in Lymphoma Symptoms According to FACT-Lym Subscale Time to progression is defined as the time from randomization to the first documentation of a 3-point decrease (clinically meaningful change) from baseline. Baseline (Cycle 1 [each cycle is 21 days]), Cycles 2, 3, 5, and 7; 28 days after last dose; and every 2 months during follow up (up to 49 months)
Secondary Stage 2: Change from Baseline in Peripheral Neuropathy According to FACT/GOG-NTX-12 Subscale Score FACT/GOG-Ntx12 is a 12-item self-reported questionnaire designed to measure chemotherapy-induced peripheral neuropathy and contains 12 items, covering sensory neuropathy, motor neuropathy, hearing neuropathy, and dysfunction associated with neuropathy. It is answered using a 5-point scale ranging from 0 = "not at all" to 4 = "very much". 0 = Not at all, 1 = a little bit, 2 = somewhat, 3 = quite a bit, and 4 = Very much. FACT/GOG-Ntx12 subscale scores can be calculated with higher scores reflective of a better outcome. Baseline (Cycle 1 [each cycle is 21 days]), Cycles 2, 3, 5, and 7; 28 days after last dose; and every 2 months during follow up (up to 49 months)
Secondary Stage 2: Percentage of Participants with Adverse Events (AEs) From randomization in RCT until up to 34 months
Secondary Stage 2: Percentage of Participants with Polatuzumab Vedotin Dose Interruptions and Dose Reductions From baseline in RCT up to approx. 34 months
Secondary Stage 2: Polatuzumab Vedotin Dose Intensity Dose intensity is defined as the ratio of actual dose administered versus intended dose. From baseline in RCT up to approx. 34 months
Secondary Stage 2: Percentage of Participants with Peripheral Neuropathy Peripheral neuropathy will be measured by the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity 12-Item Scale (FACT-GOG/Ntx12). FACT-GOG/Ntx12 is a 12-item self-reported questionnaire designed to measure chemotherapy-induced peripheral neuropathy and contains 12 items, covering sensory neuropathy, motor neuropathy, hearing neuropathy, and dysfunction associated with neuropathy. From randomization in RCT until up to 49 months
Secondary Stage 2: Percentage of Participants with Anti-drug Antibodies (ADAs) to Polatuzumab Vedotin at Baseline Baseline (Day 1 of Stage 2)
Secondary Stage 2: Percentage of Participants with Anti-drug Antibodies (ADAs) to Polatuzumab Vedotin Post-Baseline Baseline (Day 1 of Stage 2) up until Month 2 of the Post-Treatment Follow-up period (up to approx. 34 months)
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